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Intraperitoneal Pemetrexed, Cisplatin, and Paclitaxel as First-Line Therapy in Treating Women With Stage III Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
Sponsors and Collaborators: University of Arizona
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00702299
  Purpose

RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin and paclitaxel and giving them in different ways may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal pemetrexed when given together with intraperitoneal cisplatin and paclitaxel in treating patients with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Drug: cisplatin
Drug: paclitaxel
Drug: pemetrexed disodium
Procedure: biologic sample preservation procedure
Procedure: high performance liquid chromatography
Procedure: mass spectrometry
Procedure: pharmacological study
Phase I

MedlinePlus related topics: Cancer Ovarian Cancer
Drug Information available for: Cisplatin Paclitaxel Pemetrexed disodium Pemetrexed
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase I Open Label Trial of Alimta® Plus Cisplatin and Paclitaxel Given Intraperitoneally (IP) as First Line Treatment for Women With Stage III Ovarian Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose [ Designated as safety issue: Yes ]
  • Percentage of patients who complete at least 6 courses of therapy at the determined maximum tolerated dose [ Designated as safety issue: No ]
  • Toxicity and tolerability as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival at 18 months as assessed by CA-125 [ Designated as safety issue: No ]
  • Median overall survival [ Designated as safety issue: No ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2007
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum-tolerated dose (MTD) of combination therapy comprising intraperitoneal (IP) pemetrexed disodium in combination with IP cisplatin and paclitaxel in patients with optimally debulked stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer in relation to the percentage of patients completing at least 6 courses of treatment.
  • To determine the toxicity and the tolerability of this regimen in these patients.

Secondary

  • To observe 80% of these patients progression free at 18 months after initiation of chemotherapy.
  • To determine, as an exploratory endpoint, the median overall survival of patients treated with this regimen.
  • To investigate the pharmacokinetics of this regimen at the determined MTD in these patients.
  • To conduct correlative studies on tumor tissue and blood from these patients.

OUTLINE: This is a dose-escalation study of pemetrexed disodium.

Patients receive pemetrexed disodium intraperitoneally (IP) on day 1, cisplatin IP on day 2, and paclitaxel IP on day 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. At least 10 patients are treated at the maximum-tolerated dose (MTD).

Whole blood samples and tumor tissue specimens are obtained from patients at baseline and banked for future DNA, RNA, and protein studies related to prediction of disease progression and treatment resistance. Plasma and intraperitoneal fluid samples may also be collected from patients treated at the MTD for pharmacokinetic analysis of plasma concentrations of pemetrexed disodium by high-performance liquid chromatography (HPLC) or mass spectrometry-HPLC.

After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or pathologically confirmed ovarian epithelial carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma

    • Stage III disease
  • Meets 1 of the following criteria:

    • No prior treatment and no more than 6 months since primary surgery
    • Platinum-sensitive at second-look surgery with no prior cisplatin therapy
  • Must have been optimally debulked to less than 2-cm residual individual tumor plaques or, if suboptimally debulked at first surgery, had chemical debulking
  • No mixed Müllerian tumor or borderline ovarian tumor
  • No CNS or brain metastases

PATIENT CHARACTERISTICS:

  • GOG performance status 0-2
  • WBC ≥ 3,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Serum bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine clearance ≥ 45 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 3 months after discontinuation of study drug
  • No psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol
  • No unstable or preexisting major medical conditions, except cancer-related abnormalities
  • No medical life-threatening complications of their malignancies
  • No known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV)
  • No serious active uncontrolled infections
  • No inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg on antihypertensive medications)
  • No New York Heart Association grade II-IV congestive heart failure
  • No weight loss between 5 to ≤ 10% within the past 14 days that is not related to ascites or paracentesis
  • No prior hypertensive crisis or hypertensive encephalopathy
  • No myocardial infarction, cerebrovascular accident, transient ischemic attack, or unstable angina within the past 6 months
  • No evidence of uncontrollable nausea
  • No clinically significant or symptomatic peripheral vascular disease (e.g., aortic aneurysm or aortic dissection)
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
  • No pre-existing clinically significant hearing loss
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or adequately treated stage I or II cancer from which the patient is in complete remission
  • No known hypersensitivity to any component of pemetrexed disodium
  • Able to take folic acid, vitamin B_12, and dexamethasone according to protocol
  • No presence of third-space fluid that cannot be controlled by drainage
  • No inability to comply with study and/or follow-up procedures

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • May have received up to 4 courses of carboplatin and paclitaxel IV as neoadjuvant chemotherapy for advanced, unresectable disease
  • Concurrent low-dose aspirin therapy (i.e., 325 mg/day) allowed
  • Concurrent ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) with short elimination half-lives allowed provided ≥ 1 of the following criteria is met:

    • Creatinine clearance (CrCl) > 80 mL/min (i.e., normal renal function)
    • CrCl 45-79 mL/min (i.e., mild to moderate renal insufficiency) AND NSAID dosing interrupted for a period of 2 days before, during, and 2 days after administration of pemetrexed disodium
  • Concurrent NSAIDs or salicylates with long half-lives (e.g., naproxen, piroxicam, diflunisal, or nabumetone) allowed provided NSAID dosing is interrupted for at least 5 days before, during, and 2 days after administration of pemetrexed disodium
  • No concurrent antineoplastic or antitumor agents not part of the study therapy (i.e., chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy)
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00702299

Locations
United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center Recruiting
Tucson, Arizona, United States, 85724-5024
Contact: Clinical Trials Office - Arizona Cancer Center at University o     520-626-9008        
Sponsors and Collaborators
University of Arizona
Investigators
Study Chair: Setsuko K. Chambers, MD University of Arizona
Principal Investigator: David S. Alberts, MD University of Arizona
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000597792, UARIZ-07-0638-04, UARIZ-SRC-18183, LILLY-UARIZ-07-0638-04, UARIZ-BIO07074
Study First Received: June 19, 2008
Last Updated: December 2, 2008
ClinicalTrials.gov Identifier: NCT00702299  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage III ovarian epithelial cancer
recurrent ovarian epithelial cancer
peritoneal cavity cancer
fallopian tube cancer

Study placed in the following topic categories:
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Ovarian epithelial cancer
Dental Caries
Genital Diseases, Female
Cisplatin
Peritoneal Diseases
Endocrine Gland Neoplasms
Ovarian cancer
Ovarian Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases
Abdominal Neoplasms
Recurrence
Fallopian Tube Neoplasms
Fallopian Tube Diseases
Folic Acid
Pemetrexed
Digestive System Diseases
Paclitaxel
Gastrointestinal Neoplasms
Peritoneal Neoplasms
Fallopian tube cancer
Endocrinopathy

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Pharmacologic Actions
Adnexal Diseases
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 15, 2009